• International Journal of Stem Cells
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• 제10권1호
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• pp.1-11
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• 2017

Human cardiomyocytes (CMs) cease to proliferate and remain terminally differentiated thereafter, when humans reach the mid-20s. Thus, any damages sustained by myocardium tissue are irreversible, and they require medical interventions to regain functionality. To date, new surgical procedures and drugs have been developed, albeit with limited success, to treat various heart diseases including myocardial infarction. Hence, there is a pressing need to develop more effective treatment methods to address the increasing mortality rate of the heart diseases. Functional CMs are not only an important in vitro cellular tool to model various types of heart diseases for drug development, but they are also a promising therapeutic agent for cell therapy. However, the limited proliferative capacity entails difficulties in acquiring functional CMs in the scale that is required for pathological studies and cell therapy development. Stem cells, human pluripotent stem cells (hPSCs) in particular, have been considered as an unlimited cellular source for providing functional CMs for various applications. Notable progress has already been made: the first clinical trials of hPSCs derived CMs (hPSC-CMs) for treating myocardial infarction was approved in 2015, and their potential use in disease modeling and drug discovery is being fully explored. This concise review gives an account of current development of differentiation, purification and maturation techniques for hPSC-CMs, and their application in cell therapy development and pharmaceutical industries will be discussed with the latest experimental evidence.

• BMB Reports
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• 제56권9호
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• pp.482-487
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• 2023

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.

• 한국의학물리학회지:의학물리
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• 제23권1호
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• pp.8-14
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• 2012

4차원 방사선치료시 환자의 정확한 호흡 조절을 위한 바이오피드백 시스템의 개발을 위해 IR (Infra-red) 카메라 뿐만아니라 일반 카메라에서 얻는 영상에서 표적의 움직임을 추적하는 최적화된 추적 알고리즘을 찾고자 한다. 본 연구에서는 LabVIEW 2010을 사용해서 시스템을 구성하였다. 모션팬톰(motimo Phantom)의 움직임을 카메라 (IR 카메라와 일반 카메라)를 통하여 영상을 획득하고 영상처리를 거친 후 ROI (Region of interest)를 설정하여, 영상에서 지정한 ROI와 패턴 매치된 점의 상하의 움직임만 좌표로 기록하였다. 영상처리에는 문턱값을 사용하여 이진화된 영상을 만들고 Sobel, Prewitt, Differentiation, Sigma, Gradient, Roberts 등의 여러 윤곽선 강조방법들을 적용한 후에 영상을 합하여 사용했다. 다양한 방법들의 성능을 객관적으로 평가하기 위한 인자로 'score' 값을 정의하여 성능을 비교하였다. 모든 방법들을 최대한 같은 조건에서 비교하기 위해서 5분씩 3번 반복하여 측정하여 ASCII 파일로 저장하여 저장된 'score' 값의 평균값과 표준편차를 구하여 비교하였다. 문턱값만을 적용한 영상의 score는 706이고 표준편차는 84였다. 윤곽선강조를 사용한 알고리즘들의 score와 표준편차는 각각 Sobel 794와 64, Differentiation 770과 101, Gradient는 754과 85, Prewitt 763과 75, Roberts 777와 93, Sigma 822와 62였다. 가장 좋은 효율을 보인 알고리즘은 Sigma방법이였다. 추적 효율이 가장 좋게 나온 Sigma방법을 이용해서 호흡을 조절하여 호흡동조 방사선치료를 시행할 때 카메라(IR 카메라 및 일반 카메라)상의 점 추적에 대한 정확도의 증가로 치료 효율을 높일 수 있을 것이라 기대된다.

• Investigative Magnetic Resonance Imaging
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• 제18권2호
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• pp.120-132
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• 2014

목적: 원발성 뇌종양환자에서 방사선 치료 후 추적 자기공명영상에서 새로 생긴 조영증강 뇌병변에 대해 종양재발과 지연성 방사선치료연관변화의 감별에 있어서 확산강조영상 (DWI), 역동적조영관류영상 (DSC PWI), 자화율강조영상 (SWI)의 진단적 가치를 서로 비교하고자 한다. 대상과 방법: 원발성 뇌종양으로 이전에 방사선치료를 받았던 환자 중, 방사선치료 종료 최소 1년 이후에 추적 자기공명영상에서 새롭게 조영증강 되는 병변을 가진 24명의 환자를 대상으로 연구하였다. 새롭게 조영증강 되는 병변은 14명의 종양재발과 10명의 방사선치료연관변화로 확인되었다. 종양재발과 방사선치료연관변화 두 환자 군의 여러변수들은 비대응표본 t 검정을 실시하여 비교 분석하였다. 다중변수 로지스틱 회귀 분석을 이용하여 DWI, DSC PWI, SWI 각 영상의 정량 분석을 통해 얻은 apparent diffusion coefficient (ADC), normalized cerebral blood volume (nCBV), proportion of dark signal intensity (proSWI) 값 중 두 군을 감별해 내는 최상의 예측 변수 (best predictor)를 정하였다. 이후 수신자 조작 특성 (Receiver operating characteristics, ROC) 분석을 통하여 best predictor의 정확도, 민감도, 특이도를 평가하였다. 결과: 방사선치료연관변화 군과 비교하여 종양재발 군에서 평균 nCBV 값이 유의하게 높았고 (P=.004), 평균 proSWI 값은 유의하게 낮았다 (P<.001). 반면, 평균 ADC 값은 두 군간에 유의한 차이를 보이지 않았다. 다중변수 로지스틱 회귀 분석 결과 proSWI 값만이 통계적으로 유의한, 감별 가능한 독립변수였으며, 민감도, 특이도, 정확도는 각각 78.6% (11 of 14), 100% (10 of 10), 87.5% (21 of 24) 였다. 결론: 뇌종양 환자에서 방사선치료 종료 최소 1년 이후에 새로 보이는 조영증강 병변의 감별에 있어 proSWI 값이 가장 중요한 변수인 것으로 나타났다.

• Bulletin of the Korean Chemical Society
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• 제31권7호
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• pp.2019-2024
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• 2010

Insulin-like growth factor binding protein 5 (IGFBP-5) plays an important role in controlling cell survival, differentiation and apoptosis. Apoptosis can be induced by an extrinsic pathway involving the ligand-mediated activation of death receptors such as tumor necrosis factor receptor 1 (TNFR1). To determine whether IGFBP-5 and TNFR1 interact as members of the same apoptosis pathway, recombinant IGFBP-5 and TNFR1 were isolated. The expression and purification of the full-length TNFR1 and truncated IGFBP-5 proteins were successfully performed in E. coli. The binding of both IGFBP-5 and TNFR1 proteins was detected by surface plasmon resonance spectroscopy (BIAcore), fluorescence measurement, electron microscopy, and size-exclusion column (SEC) chromatography. IGFBP-5 indeed binds to TNFR1 with an apparent $K_D$ of 9 nM. After measuring the fluorescence emission spectra of purified IGFBP-5 and TNFR1, it was found that the tight interaction of these proteins is accompanied by significant conformational changes of one or both. These results indicate that IGFBP-5 acts potently as a novel ligand for TNFR1.

• 환경생물
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• 제23권2호
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• pp.152-156
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• 2005

Ionizing radiation is a well- known therapy factor for human carcinoma cells. Genotoxic stress mediates cell cycle control, transcription and cellular signaling. In this work, we have used a microarray hybridization approach to characterize the cell type-specific transcriptional response of human carcinoma MCF-7 and HeLa cell line to $\gamma-radiation$, such as 4Gy 4hr. We found that exposure to $\gamma-ray$ alters by at least a $log_2$ factor of 1.0 the expression of known genes. Of the 27 genes affected by irradiation, 11 are down- regulated in MCF-7 cells and 2 genes induced by radiation,15 are repressed in HeLa cells. Many genes were involved in known damage- response pathways for cell cycling, transcription factor and cellular signaling response. However, in MCF-7 cells, we observed gene expression pattern in chromatin, apoptosis, stress, differentiation, cytokine, metabolism, ribosome and calcium. In HeLa cells, it showed clearly the expression changes in adhesion and migration, lysosome, brain, genome instability and translation. These insights reveal new therapy directions for studying the human carcinoma cell response to radiation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권1호
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• pp.65-68
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• 2001

The major manifestations of aplastic anemia are characterized by persistent bone marrow aplasia and peripheral pancytopenia due to defective stem cells in which differentiation is not curtailed or preferential elimination of stem cells with self-renewal capacity, which results in serious complications such as bleeding and infection. Recent advances in the therapeutic modalities, such as bone marrow transplantation and immunosuppressive therapy, and in supportive measures as component transfusion and infection control with better quality of antibiotics resulted in an improved survival and subsequently increased possibility of complications which need surgical intervention. Considering the fact that surgery may not only control complications, but offers the opportunity to give effective therapy for aplastic anemia and therefore improves chances for survival, it is strongly suggested that active surgical intervention should be performed. We report a case of patient with aplastic anemia who had been performed surgical intervention of partial maxillectomy for the squamous cell carcinoma on maxilla without serious complications during perioperative and postoperative period.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제30권2호
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• pp.136-142
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• 2004

Malignant fibrous histiocytoma(MFH) is the malignant part of mesenchymal cell-originated tumor, which is supposed that the tumor is presented various histologic features consisted of fibrosarcomatic and histiocytic portions. When the tumor is arisen in the head and neck region, the most affected sites are the nasal cavity and paranasal sinuses, and secondly the maxillary alveolar bone is occasionally influenced. Therefore, MFH can readily involve the adjacent alveolar bone. The treatment of MFH in the head and neck is various, that is, the involved sites and the differentiation of tumor must be considered when the tumor is treated. The treatment protocols are subjected to general ones of soft tissue sarcoma, and simple or combination therapy is used in the surgery, chemotherapy and radiation therapy. So, we report a clinical case of chemotherapy involving intraarterial chemotherapy, and surgery of malignant fibrous histiocytoma(MFH) in the maxilla, with review of the literature.

• BMB Reports
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• 제50권3호
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• pp.117-125
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• 2017

Most of the cancers are still incurable human diseases. According to recent findings, especially targeting cancer stem cells (CSCs) is the most promising therapeutic strategy. CSCs take charge of a cancer hierarchy, harboring stem cell-like properties involving self-renewal and aberrant differentiation potential. Most of all, the presence of CSCs is closely associated with tumorigenesis and therapeutic resistance. Despite the numerous efforts to target CSCs, current anti-cancer therapies are still impeded by CSC-derived cancer malignancies; increased metastases, tumor recurrence, and even acquired resistance against the anti-CSC therapies developed in experimental models. One of the most forceful underlying reasons is a "cancer heterogeneity" due to "CSC plasticity". A comprehensive understanding of CSC-derived heterogeneity will provide novel insights into the establishment of efficient targeting strategies to eliminate CSCs. Here, we introduce findings on mechanisms of CSC reprogramming and CSC plasticity, which give rise to phenotypically varied CSCs. Also, we suggest concepts to improve CSC-targeted therapy in order to overcome therapeutic resistance caused by CSC plasticity and heterogeneity.

• 대한한의학회지
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• 제19권1호
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• pp.470-499
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• 1998

For the purpose of designing more successful cancer research, the strategy for cancer study in the field of Traditional Korean Medicine(TKM) during the 21th century was examined from the analysis of trends on cancer study in traditional korean medicine. The results were summarized as follows: 1. So far cancer research in TKM was chiefly done on cytotoxicity, side-effects by chemotherapy, tumor immunology, apoptosis, survival time with S-180 and pulmonary colonization assay and also clonogenic assay, cell adhesion assay, angiogenesis, cell-differentiation and side-effect by radiotherapy were partly performed. 2. It may be ideal that we should study synergistic effect between constituent drugs of prescriptions, tumor immunology, combined therapy between western and oriental medicines by reducing side-effect by radiotherapy and chemotherapy and antimetastasis according to the characteristics of oriental medicine chiefly and also supplement the studies on molecular biology, gene therapy, angiogensis and signal transduction. 3. We had better do specific-field research in cooperation between oriental medical colleges and Korea Institute of Oriental Medicine(KIOM) as well as study a target cancers such as hepatic cancer, pulmonary cancer and gastric cancer more intensively than all cancers domestically. 4. Our country must keep communication with China having many clinical data, Taiwan chiefly doing the combined tharapy between oriental and western medicines, Japan having done basic study actively on cancer.